Kumaki F, Kawai T, Hiroi S, Shinomiya N, Ozeki Y, Ferrans V J, Torikata C
Department of Pathology, National Defense Medical College, Tokorozawa, Japan.
Hum Pathol. 2001 Feb;32(2):188-95. doi: 10.1053/hupa.2001.21567.
The aim of this study was to evaluate the usefulness of determination of telomerase activity and expression of human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) for the diagnosis of lung carcinomas. The tissues studied consisted of 115 carcinomas and adjacent nonneoplastic lung, which were removed surgically without previous chemotherapy or radiotherapy. Telomerase activity was determined using a semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay. The results obtained were classified into high and low telomerase groups. Localization of expression was examined by using in situ hybridization and immunohistochemistry. The correlation between telomerase activity in lung carcinoma and clinicopathologic features, including prognosis, was investigated. Telomerase activity in lung carcinomas was detected in 107 of 115 (93%) lung carcinomas, but not in any adjacent noncancerous tissues, and was significantly higher in small cell carcinoma than in any other histologic type. This activity also was significantly higher in poorly differentiated than in well-differentiated squamous cell carcinomas and adenocarcinomas. The overall survival rate (P =.020) was significantly lower in the high telomerase group. Messenger RNAs for hTERC and hTERT were mainly detected in the cytoplasm of cancer cells by in situ hybridization, and TERT protein was localized in the nuclei of these cells by immunohistochemical staining. Determinations of telomerase activity by in situ hybridization, immunohistochemistry, and TRAP assay are useful for evaluating the diagnosis and prognosis of lung carcinomas.
本研究的目的是评估端粒酶活性测定以及人端粒酶RNA组分(hTERC)和人端粒酶逆转录酶(hTERT)表达对于肺癌诊断的有用性。所研究的组织包括115例癌组织及相邻的非肿瘤性肺组织,这些组织均为手术切除,术前未接受化疗或放疗。使用基于半定量聚合酶链反应的端粒重复序列扩增法(TRAP)测定端粒酶活性。将所得结果分为端粒酶高表达组和低表达组。通过原位杂交和免疫组织化学检测表达的定位。研究肺癌中端粒酶活性与包括预后在内的临床病理特征之间的相关性。115例肺癌中有107例(93%)检测到端粒酶活性,而在任何相邻的非癌组织中均未检测到,小细胞癌中的端粒酶活性显著高于任何其他组织学类型。在低分化鳞状细胞癌和腺癌中,端粒酶活性也显著高于高分化者。端粒酶高表达组的总生存率(P = 0.020)显著较低。通过原位杂交、免疫组织化学和TRAP测定法检测端粒酶活性,对于评估肺癌的诊断和预后是有用的。